This project was undertaken to elucidate biochemical and immunological aspects of myelin disorders associated with neuro-AIDS. In the central nervous system these include diffuse myelin pallor (DMP) (decreased staining with Luxol fast blue), vacuolar myelopathy and multifocal demyelination. In the peripheral nervous system, this covers a demyelinating peripheral neuropathy. Postmortem subcortical white matter samples from AIDS patients with and without dementia were analyzed for quantitative and qualitative alterations of myelin proteins, including myelin-associated glycoprotein (MAG), myelin basic protein, proteolipid protein and 2',3'-cyclic nucleotide 3'-phosphodiesterase. The biochemical results were correlated with histological and immunocytochemical observations made by our collaborators at Johns Hopkins University on adjacent sections of tissue. DMP was detected histologically in about one-half of demented patients and one-fourth of the nondemented patients. However, electron microscopic, immunocytochemical and biochemical analyses of white matter indicated little or no loss of myelin proteins in areas of prominent DMP. On the other hand, substantial conversion of MAG to a proteolytic cleavage product (dMAG) was observed in some of the AIDS samples, as had previously been found in many samples from multiple sclerosis brain (see Z01 NS 02848-03 LMCN). Astrocytic hypertrophy was found in some of the AIDS patients both histologically and by increased levels of glial fibrillary acidic protein detected biochemically. Significant accumulation of serum proteins was detected immunocytochemically in white matter of many of the AIDS cases, especially the demented ones. This was supported biochemically by the presence of variable levels of haptoglobin on Western blots of AIDS samples but not of control samples. Overall, the results provide little evidence for significant demyelination or myelin pathology in subcortical white matter of AIDS brain, but suggest that blood brain barrier perturbation may contribute to CNS pathology in AIDS and AIDS dementia. The relationship of blood brain barrier breakdown to the proteolytic MAG/dMAG conversion observed in multiple sclerosis and AIDS brain is under investigation.